High cholesterol tied to Alzheimer brain "plaques"

NEW YORK (Reuters Health) - Middle-aged and older adults with high cholesterol may have an increased likelihood of developing protein deposits in the brain that are connected to Alzheimer's disease, a new study suggests.

The findings, the researchers say, do not prove that high cholesterol is a risk factor for Alzheimer's disease itself.

But they raise the possibility that keeping cholesterol in check can help prevent brain plaques later in life, according to Dr. Kensuke Sasaki of Kyushu University in Japan, who worked on the study.

And that, in turn, could affect the risk of developing Alzheimer's disease, Sasaki told Reuters Health in an email.

The study involved autopsied brain tissue from 147 Japanese adults who died sometime between 1998 and 2003.

One-third had been diagnosed with dementia before they died. All had had their cholesterol measured back in 1988, when they were between the ages of 40 and 79, and free of dementia symptoms.

Overall, the researchers found, brain "plaques" -- abnormal protein deposits that form between nerve cells -- were more common among the one-quarter of people who'd had the highest cholesterol levels in 1988.

In that group, whose total cholesterol levels were 5.8 mmol/L -- about 224 milligrams per deciliter (mg/dL) -- or higher, 86 percent had brain plaques at autopsy.

That compared with 62 percent of people who'd had lower total cholesterol levels, around 186 mg/dL or less, at the study's outset.

The researchers then accounted for other factors known to be tied to Alzheimer's disease -- including age, history of stroke and whether people carried a particular gene variant linked to the disease. They found that people with the highest cholesterol were almost 25 times more likely to have brain plaques at autopsy than those with lower cholesterol.

Brain plaques, along with other abnormal structures called "tangles," are considered the hallmark physical features of Alzheimer's disease. But not everyone with brain plaques develops Alzheimer's; in some cases, the plaques seem to be simply a product of aging.

And past studies that looked for a link between having high cholesterol and later being diagnosed with Alzheimer's have come to mixed conclusions, according to Sasaki.

That relationship does appear stronger, however, when studies focus on cholesterol levels closer to mid-life, when people are in their 40s, 50s or 60s, said Dr. Constantine Lyketsos, director of the Memory and Alzheimer's Treatment Center at Johns Hopkins University in Baltimore.

But Lyketsos, who was not involved in the current study, pointed to what he thinks is the leading possibility: that cholesterol is serving as a sign of overall vascular disease affecting the brain.

A number of studies have found that some of the same factors that damage blood vessels and contribute to heart disease -- like diabetes and high blood pressure -- are also related to an increased Alzheimer's risk.

This study, Lyketsos said, offers more-direct evidence by looking at two biological measures: cholesterol levels in the blood and later amounts of plaque in the brain.

Alzheimer's is thought to affect 26 million people worldwide, and experts estimate that as people live longer, that number could reach 66 million by 2030.

Old age is the most reliable risk factor, as most cases Alzheimer's are diagnosed after age 60. Genetics is also thought to play a key role: most famously, people with a specific version of a gene called APOE -- the form known as APOE4 -- have a higher risk of developing Alzheimer's.

But researchers have also identified several other genes that may be connected to the brain disease, including genes involved in inflammation, the movement of protein within cells and the transport of cholesterol.

For now, Lyketsos said the findings underscore what we should all be doing anyway: keeping cholesterol levels in check.

"People should already be concerned about high cholesterol because of heart disease," Lyketsos noted.

"We know it isn't good," he said, "and this is one more possible reason to control your cholesterol."

In general, experts recommend that people rein in cholesterol by maintaining a healthy weight, exercising and making diet changes, and taking medication if necessary.

Total cholesterol levels below 200 mg/dL are considered desirable for reducing the risk of heart disease.

But whether keeping cholesterol or other heart risk factors in check will curb your risk of Alzheimer's remains unknown.

Studies have failed to show that cholesterol-lowering statins help cut the risk of Alzheimer's. And in May, a U.S. government panel concluded there is no strong evidence yet that diet and lifestyle measures affect people's risk of the disease (see Reuters Health story of May 10, 2011).